Molecular docking studies for the identifications of novel antimicrobial compounds targeting of staphylococcus aureus

This work  include several advanced molecular docking tools to study the interactions of our newly synthesized 1,3,4-thiadiazole  derivatives in the active site of penicillin binding protein and DNA gyrase against Staphylococcus aureus, the enzymes targeted for antimicrobial agents. Results such as MolDock scores, binding energies, residue binding distances, etc. were identified and discussed in this present research. The molecules with best docking results were selected in order to calculate drug likeness and bioavailability using Molinspiration software. All the compounds obey Lipinski’s rule and its extension and showed drug likeness. The pharmacokinetic parameters study was done using the AdmetSAR to display ADME and toxicity properties of these antimicrobial

Molecular docking studies and ADMET properties of new 1.2.3 triazole derivatives for anti-breast cancer activity

International audienceAromatase inhibitors have emerged as promising candidates for the treatment of breast cancer, which represents the second most prevalent cancer in females and is considered as the second leading cause of death among women. Inhibitory effect of 1.2.3 triazole were evaluated on the human aromatase enzyme and compared with the Letrozole (LTZ), the most potent inhibitor of aromatase, which is used as anti-estrogen for breast cancer treatment. For this study MOLEGRO software was used to calculate inhibition energy (IE) of triazoles on aromatase enzyme p450 (3EQM.PDB). As a result we suggest p450-1.2.3 triazole complex has higher stability and stronger affinity because p450 shows more favorable interaction energy. Moreover, Molinspiration and ADMETSAR web servers used to calculate ADMET and physicochemical properties of the target compounds. © 2018 American Scientific Publishers

Pharmacoinformatics and Breed-Based De Novo Hybridization Studies to Develop New Neuraminidase Inhibitors as Potential Anti-Influenza Agents

Influenza represents a profoundly transmissible viral ailment primarily afflicting the respiratory system. Neuraminidase inhibitors constitute a class of antiviral therapeutics employed in the management of influenza. These inhibitors impede the liberation of the viral neuraminidase protein, thereby impeding viral dissemination from the infected cell to host cells. As such, neuraminidase has emerged as a pivotal target for mitigating influenza and its associated complications. Here, we apply a de novo hybridization approach based on a breed-centric methodology to elucidate novel neuraminidase inhibitors. The breed technique amalgamates established ligand frameworks with the shared target, neuraminidase, resulting in innovative inhibitor constructs. Molecular docking analysis revealed that the seven synthesized breed molecules (designated Breeds 1–7) formed more robust complexes with the neuraminidase receptor than conventional clinical neuraminidase inhibitors such as zanamivir, oseltamivir, and peramivir. Pharmacokinetic evaluations of the seven breed molecules (Breeds 1–7) demonstrated favorable bioavailability and optimal permeability, all falling within the specified parameters for human application. Molecular dynamics simulations spanning 100 nanoseconds corroborated the stability of these breed molecules within the active site of neuraminidase, shedding light on their structural dynamics. Binding energy assessments, which were conducted through MM-PBSA analysis, substantiated the enduring complexes formed by the seven types of molecules and the neuraminidase receptor. Last, the investigation employed a reaction-based enumeration technique to ascertain the synthetic pathways for the synthesis of the seven breed molecules